It is uncertain whether an insidious, but significant, build-up of physical dependence to benzodiazepines occurs as a result of prolonged chronic dosing in the therapeutic range. This will be ascertained by measuring fine motor control capability during acute and chronic diazepam dosing and after withdrawal. Performance will be correlated with blood and brain levels of the drug and its active metabolites in this and some of the ensuing studies. Surveys of groups of methadone-maintained patients reveal frequent abuse of benzodiazepines with some heavy usage producing physical dependence. Oral diazepam can function as a reinforcing agent in former sedative-drug abusers, but does not in normal outpatient groups. Special conditions are required before chlordiazepoxide becomes a reinforcer for animals as well. The investigation of such conditions, especially schedule-induced polydipsia and conflict situations may illuminate the factors necessary for the initiation and perpetuation of substance overindulgence. The role of accruing tolerance and physical dependence as critical determinants in maintaining drug abuse is uncertain and will be evaluated. Further, conflict and stress are purported to trigger and exacerbate drug problems; hence, their efficacy in increasing schedule-induced drug-taking is of interest. Since much human substance abuse occurs by the oral route, the conditions initiating and maintaining oral overindulgence of psychoactive agents needs explication. Finally, a novel test procedure for determining the punishment-attenuating properties of the benzodiazepines and some of the new benzodiazepine-like agents will be explored. The punishment-attenuating aspect of sedative-hypnotics has been shown to correlate well with their anxiolytic potency and efficacy.